Comparative determination of the efficacy of bispyridinium oximes in paraoxon poisoning

Abstract

The inability of standard therapy to provide adequate protection against poisoning by organophosphorus compounds (pesticides and/or nerve agents) motivated us to search for new, more effective oximes. We investigated the pharmacotoxicological properties of six experimental K-oximes (K027, K033, K048, K074, K075, and K203) in vivo. The therapeutic efficacy of K-oximes (at doses of 5 or 25 % of their LD₅₀)combined with atropine was assessed in paraoxon-poisoned mice and compared with conventionally used oximes HI-6 and TMB-4. The bisoxime K074 was the most toxic (LD₅₀=21.4 mg kg^-1) to mice, while monoxime K027 was the least toxic (LD₅₀=672.8 mg kg^-1). With the exception of K033, all of the tested K-oximes showed better therapeutic efficiency than HI-6 and TMB-4. K027 and K048 stood out by demonstrating low acute toxicities and ensuring protective indices ranging from 60.0 to 100.0 LD₅₀ of paraoxon. Taking into account that these two oximes showed a similar therapeutic efficacy regardless of the applied doses, our results suggest that K027 and K048 could be perspective antidotes for paraoxon intoxication.